Phenyl derivatives of 5-nitrofuroguanamine



. PHENYL DERIVATIVES or S-NITROFURO- GUANAMINE William R. Sherman, Waukegan, Ill., assignor to Abbott Laboratories, Chicago, 11]., a corporation of Illinois No Drawing. Filed Dec. 29, 1953, Ser. No. 783,169

Claims. c1. a so-249.9

This invention relates to novel compounds represented by the formula:

In this and succeeding formulas, R represents phenyl, loweralkylphenyl, nitrophenyl or halophenyL. The term loweralkylphenyl as employed hereinrefers to a phenyl radical substituted by an alkyl group containing from 1 to 4 carbon atoms, inclusive. The term halophenyl refers to a phenyl radical substituted in the ortho, meta or para positions by chlorine, bromine, fluorine or iodine. In like manner; the nitro' group or loweralkyl group may be substituted on the phenyl ring in they ortho, meta or para positions but the ortho and para positions are preferred. These compounds are crystalline solids which are moderately soluble in many organic solvents but only slightly soluble in water. They have been found to be useful as parasiticides and are adapted to be employedin liquid and dust compositions for the control of the growth of fungi and bacteria such as Escherichia 0011'.

The new compounds may be prepared by the reaction resented by the formula:

The reaction proceeds smoothly at temperatures of from C. to the boiling temperature of the reaction mixture. In a preferred method of operation, the reaction is carried out in the presence of an inert organic solvent such as ethyleneglycolmonomethylether or ethanol. Good results are obtained when employing substantially equimolecular proportions of the reactants.

In carrying out the reaction, the methyl 5-m'tro-2- furoate and aryl diguanide are dissolved in the solvent and the resulting mixture allowed to stand at or about room temperature or heated preferably at the boiling temperature and under reflux for a sufficient period of time to complete the reaction. The precipitate which forms during the reaction or upon cooling the reaction mixture is separated in a conventional manner such as by filtration or decantat-ion. The desired triazine product may be further purified by recrystallization from a suitable organic solvent.

The following examples are presented to illustrate but not limit the invention:

2 EXAMPLE I 2-amino-4-anilin0-6-(S-nitro-Z-furyl)-1,3,5-triazine CH-CH N out-( i L/ O NH O o l l'Hz N -phenyldiguanide (17.7 grams, 0.10 mole) and methyl S-nitro-Z-furoate (17.1 grams, 0.10 mole) were dissolved in ml. of ethyleneglycolmonomethylether and the resulting mixture heated on a steam bath for 3.5 hours. The reaction mixture was then allowed to stand for three days during which time the desired 2- amino-4-anilino-6-(5-nitro-2-furyl)-l,3,5-triazine precipitated as a crystalline solid. This product was separated by filtration and after successive recrystallizations from dimethylformamide and butanol melted at 259 260 C.

Analysis.-Calcd. for C H O N C=52.35%; H: 3.38%; N=28.=18%. Found: C=52.53%; H=3.50%;

EXAMPLE :1

OH-CH Methyl S nitro-Z-furoate (8.55 grams; 0.05 mole) and N -(orthotoly1)-diguanide (9.95 grams, 0.05 mole) were dissolved in 30' ml. of ethyleneglycolmonornethylether and the resulting mixture allowed to stand at room temperature for five days. The solid which precipitated was separated by filtration and washed with alcohol to obtain 2'-amin0-4- (orthotoluidino) -6-( 5-nitro-2-turyl) -1,3,5- triazine which after recrystallization from butanol was found to melt at 257 C. with decomposition.

Analysis.Calcd. for C H O N C=53.84%; H: Found: C=52.53%; H=3.50%;

EXAMPLE III 2 amino 4 (paranitronanilino) 6 (5 nitro 2- furyl)-1,3,5-triazine A solution of N -(paranitropheny1)-diguanide (12.93 grams, 0.05 mole) and methyl 5-nitro-2-furoate (8.55 grams, 0.058 mole) in 100 ml. of absolute ethanol was heated at the boiling temperature and under reflux for 6 hours. The solid which precipitated was removed by filtration, crystallized from a dimethylformamide-water mixture and dried under vacuum at a temperature of 153 C. As a result of these operations, there was obtained 2-amino-4- (paranitroanilino) -6-( 5-nitro-2-furyl) 1,3,5-t-n'azine which melted at 339 C.

Analysis.--Ca1cd. for C H O N C=45.48% ;H: 2.65%; N=28.56%. Found: C=45.25%; H=2.86%; N=28.72.

3 EXAMPLE IV 2 amino 4 (parachloroanilino) 6 nitro 2- furyl) ,3,5-triazine EXAMPLE V 2 amino 4 (parabromoanilino) 6 (5 nitro 2- ]uryl -1,3 ,5 triazine This compound is prepared by the reaction of N (parabromophenyl)-diguanide and methyl S-nitro-Z-furoate in the same manner as that described in Example IV. The product has a molecular weight of 377.

By employing the procedure described in the foregoing examples, other triazine compounds can be prepared as follows:

2 amino 4 (paratoluidino) 6 (5 nitro --2 furyl)- 1,3,5-triazine,

2 amino 4 (orthonitroanilino) 6 (5 nitro 2- furyl) -1,3 ,5 -triazine,

2 amino 4 (orthochloroanilino) 6 (5 nitro 2- furyl) -1,3 ,5 -triazine,

2 amino 4 (metabromoanilino) 6 (5 nitro 2-.

furyl)-1,3,5-triazine, 2 amino 4 (metatoluidino) 6 (5 nitro 2 furyl),-

1,3,5-triazine, and

2 amino 4 (parafluoroanilino) 6 (5 nitro 2- furyl)-1,3,5-triazine by the reaction of methyl 5-nitro- Z-furoate with 4 N (paratolyl) -diguanide, N orthonitrophenyl) -digu anide, N orthochlorophenyl) -diguanide, N (metabromophenyl) -diguanide, N (metatolyl) -diguanide or N (parafluorophenyl -diguanide, respectively.

The compounds of the present invention have been found to be useful particularly as antibacterial agents. For such use, the products may be dispersed in liquid or on solid carriers with or without the aid of a wetting agent and employed as sprays or dusts. In other procedures, the products may be employed as constituents of oil-in-water emulsions or water dispersions with or without the aid of wetting, dispersing or emulsifying agents. In representative operations, complete inhibition of the growth of Micrococcus pyogenes var. aureus and Escherichia coli was obtained with an aqueous composition containing 25 parts by weight of 2-amino-4-(parachloroanilino)-6-(5-nitro-2-furyl)-1,3,5-triazine per million parts by weight of ultimate mixture.

I claim: 1. A triazine compound represented by the formula:

(ILIH(I%H /N\ OiN-C o-0 \C-NHR II I N N l TH2 References Cited in the file of this patent UNITED STATES PATENTS Thurston et al Dec. 26, 1950 Schock May 5, 1959 OTHER REFERENCES Chemical Abstracts: vol. 45, p. 10302 (1951) [abstract of Ikegati, Japan J. Pharm. and Chem.,,vol. 22, pp. 293-300 (1951)].

Dunlop et al.: The Furans, ACS Monograph Series No. 119, p. 164, Reinhold Publishing Corp, 1953.

UNITED STATES PATENT OFFICE Fe CERTIFICATION OF CORRECTION Patent No. 2 953 564 September 2O 1960 I William R. Sherman It is hereby certified that error appears in the above numbered pat ent requiring correction and that the said Letters Patent should read as corrected below.

Column 2, line 45, for "3.38%; N=28. 18%, Found: C=52.53%'; H=350%; read 3,87%; N=26,9l%. Found:- C=53.78%; H=3.74%; lines 53 to 58, the center portion of the formula should appear as shown below instead of as in the patent:

column 3, line l2, for "(0.5 mole) read (005 mole) "s Signed and sealed this 9th day of May 1961.

(SEAL) Attest:

ERNEST w. SWIDER DAVID L. LADD I Attesting Officer Commissioner of Patents 

1. A TRIAZINE COMPOUND REPRESENTED BY THE FORMULA: 